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Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) increases proinflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Muscle contractions can suppress LPS/TLR4 axis activation by reducing the protein expression of TLR4 on immune cells. However, the mechanism by which muscle contractions decrease TLR4 remains undefined. Moreover, it is not clear whether muscle contractions affect TLR4 expressed on skeletal muscle cells. The purpose of this study was to uncover the nature and mechanisms by which stimulated myotube contractions using electrical pulse stimulation (EPS) as an in vitro model of skeletal muscle contractions affect TLR4 expression and intracellular signaling to combat LPS-induced muscle atrophy. C2C12 myotubes were stimulated to contract via EPS with and without subsequent LPS exposure. We then examined the isolated effects of conditioned media (CM) collected following EPS and soluble TLR4 (sTLR4) alone on LPS-induced myotube atrophy. Exposure to LPS decreased membrane-bound and sTLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, EPS decreased membrane-bound TLR4, increased sTLR4, and prevented LPS-induced signaling and myotube atrophy. CM, which contained elevated levels of sTLR4, prevented LPS-induced upregulation of atrophy-related gene transcripts muscle ring finger 1 (MuRF1) and atrogin-1 and reduced myotube atrophy. Recombinant sTLR4 added to media prevented LPS-induced myotube atrophy. In summary, our study provides the first evidence that sTLR4 has anticatabolic effects by reducing TLR4-mediated signaling and atrophy. In addition, the study reveals a novel finding, by demonstrating that stimulated myotube contractions decrease membrane-bound TLR4 and increase the secretion of sTLR4 by myotubes.NEW & NOTEWORTHY Excessive Toll-like receptor 4 (TLR4) activation causes muscle atrophy. Muscle contractions can limit TLR4 activation on immune cells, but its impact on TLR4 expressed on skeletal muscle cells remains unclear. Here, we demonstrate in C2C12 myotubes for the first time that stimulated myotube contractions reduce membrane-bound TLR4 and increase soluble TLR4, preventing TLR4-mediated signaling and myotube atrophy. Further analyses revealed soluble TLR4 independently prevents myotube atrophy, supporting a potential therapeutic role in combating TLR4-mediated atrophy.
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Lipopolisacáridos , Receptor Toll-Like 4 , Humanos , Lipopolisacáridos/toxicidad , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Transducción de Señal , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismoRESUMEN
Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including activation of the protein kinase B-mechanistic target of rapamycin (Akt-mTOR) signaling cascade. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock protein A (HSPA) and C (HSPC) families alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on HSP expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. Heat stress alone may also exert similar effects, though the responses are notably variable and require further investigation. In addition, acute heat stress in C2C12 muscle cells enhanced myotube growth and myogenic fusion, albeit to a lesser degree than growth factor-mediated hypertrophy. Though the mechanisms by which heat stress stimulates hypertrophy-related signaling and the potential mechanistic role of HSPs remain unclear, these findings provide additional evidence implicating heat stress as a novel growth stimulus when combined with resistance exercise in human skeletal muscle and alone in isolated murine muscle cells. We believe these findings will help drive further applied and mechanistic investigation into how heat stress influences muscular hypertrophy and atrophy.NEW & NOTEWORTHY We show that acute resistance exercise followed by whole body heat stress increases the expression of HSPA and increases activation of the Akt-mTOR cascade in a physically active and resistance-trained population.
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Trastornos de Estrés por Calor , Proteínas Proto-Oncogénicas c-akt , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Choque Térmico/metabolismo , Músculo Esquelético/metabolismo , Respuesta al Choque Térmico , Trastornos de Estrés por Calor/metabolismo , Hipertrofia/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Atrofia/metabolismo , Atrofia/patologíaRESUMEN
NEW FINDINGS: What is the central question of this study? What is the effect of hypobaric hypoxia on markers of exercise-induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance? Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise-induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I-FABP, LBP and CLDN-3 were correlated to exercise-induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. ABSTRACT: We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM VÌO2max${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . GI symptoms were assessed before and every 15 min during exercise. Pre- and post-exercise blood samples were assessed for intestinal fatty acid binding protein (I-FABP), claudin-3 (CLDN-3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I-FABP significantly increased from pre- to post-exercise in HYP (708 ± 191 to 1215 ± 518 pg ml-1 ; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml-1 ; P > 0.99, d = 0.27). CLDN-3 significantly increased from pre- to post-exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml-1 ; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml-1 ; P = 0.435, d = 0.45). LBP significantly increased from pre- to post-exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 µg ml-1 ; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 µg ml-1 ; P > 0.99, d = 0.32). I-FABP (d = 0.85), CLDN-3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post-exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI-FABP (r = 0.71), ΔCLDN-3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.
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Ejercicio Físico , Enfermedades Gastrointestinales , Altitud , Humanos , Hipoxia , MasculinoRESUMEN
PURPOSE: Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. METHODS: Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3 h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. RESULTS: Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3 h post-exercise in hypoxia but not control. PGC1A mRNA increased 3 h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. CONCLUSION: Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.
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Ejercicio Físico , Músculo Esquelético , Expresión Génica , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Contracción Muscular , Músculo Esquelético/fisiologíaRESUMEN
PURPOSE: The purpose of the study was to investigate the combined effect of downhill running and heat stress on muscle damage, as well as on heat strain and kidney stress during subsequent running in the heat. METHODS: In a randomized cross-over study, ten non-heat-acclimated, physically active males completed downhill running in temperate (EIMD in Temp) and hot (EIMD in Hot) conditions followed by an exercise-heat stress (HS) test after 3-h seated rest. Blood and urine samples were collected immediately pre- and post-EIMD and HS, and 24 h post-EIMD (post-24 h). Core temperature and thermal sensation were measured to evaluate heat strain. Serum creatine kinase (CK), maximal voluntary isometric contraction of the quadriceps (MVC) and perceived muscle soreness were measured to evaluate muscle damage. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels were measured to indicate acute kidney stress. RESULTS: CK, MVC and perceived soreness were not different between conditions at any timepoints. In the EIMD in Hot condition, urinary NGAL was significantly elevated from pre- to post-HS (pre-HS: 6.56 {1.53-12.24} ng/min, post-HS: 13.72 {7.67-21.46} ng/min, p = 0.034). Such elevation of NGAL or KIM-1 was not found in the EIMD in Temp condition. CONCLUSIONS: As compared with downhill running in a temperate environment, downhill running in a hot environment does not appear to aggravate muscle damage. However, elevated NGAL levels following EIMD in a hot environment suggest such exercise may increase risk of mild acute kidney injury during subsequent endurance exercise in the heat.
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Trastornos de Estrés por Calor , Músculo Esquelético , Respuesta al Choque Térmico , Humanos , Riñón , Lipocalina 2 , Masculino , Músculo Esquelético/fisiologíaRESUMEN
We investigated the effect of cardiorespiratory fitness (CRF) on the probability of achieving the verification criterion to confirm that VO2max was obtained in a sample of middle-aged to older adults. Data from twelve men and nine women (60.7±8.5 years, VO2max: 34.8±9.4 mL/kg/min) were used for analysis. Participants had their VO2max measured via a maximal graded exercise test and confirmed using a verification bout on a cycle ergometer. Logistic regression was used to evaluate the effect of CRF (VO2max) on the probability a participant would successfully achieve the verification criterion. Odds ratios are reported to quantify the effect size. No statistically significant relationship was observed between CRF and achieving the verification criterion (ß=.081, SE=.0619, Wald=1.420, p=.156). Estimated odds ratio for the effect of CRF on the verification criterion indicated an increase of 8% [Exp(ß)=1.08, 95% CI (0.96, 1.22)] in the probability of achieving the verification criterion given a one unit increase in VO2max. Each 1 mL/kg/min increase in VO2max results in an 8% increase in the chance that an individual achieves the verification criterion confirming that VO2max was obtained. Therefore, CRF is likely of practical significance and should be considered when deciding to use a verification trial.
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Capacidad Cardiovascular , Anciano , Prueba de Esfuerzo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consumo de OxígenoRESUMEN
OBJECTIVE: To assess the long-term impact of early COVID-19 lockdown phase on emergency psychiatric consultations in two psychiatric emergency departments located in Italy. METHODS: We conducted a cross-sectional study comparing the number and characteristics of emergency psychiatric consultations during post-lockdown with respect to the lockdown period. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis, information on multiple psychiatric consultations and hospitalisation were collected. RESULTS: A rise of almost 60% in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed. Emergency psychiatric consultations in the post-lockdown period were associated with lower rates of cannabis (aOR = 0.42, p = 0.011) and cocaine use (aOR = 0.39, p = 0.011). Despite a lower occurrence of two or more psychiatric consultations was observed during post-lockdown phase (aOR = 0.44, p = 0.008), subjects who had anxiety disorders (aOR = 3.91, p = 0.000) and substance intoxication or withdrawal (aOR = 6.89, p = 0.000) were more likely to present to emergency psychiatric consultations during post-lockdown period compared to the lockdown one. CONCLUSIONS: Substance intoxication or withdrawal and anxiety disorders increased after the COVID-19 lockdown. The findings of this study suggest to address more economic and professional sources to the mental health areas potentially more affected by the different phases of a pandemic.KEYPOINTSCOVID-19 pandemic and lockdown measures increased mental health unmet needs.According to our findings, a rise in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed.Patients with substance intoxication or withdrawal syndrome and anxiety disorders were significantly more likely to present to emergency psychiatric consultations during post-lockdown.Lockdown was associated with higher rates of both cannabis and cocaine use disorders as well as of multiple psychiatric consultations.Alternative strategies to improve mental health such as e-health technologies should be promoted.
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COVID-19 , Cocaína , Servicios de Urgencia Psiquiátrica , Control de Enfermedades Transmisibles , Estudios Transversales , Humanos , Italia , Pandemias , SARS-CoV-2RESUMEN
One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; â¼200%, P=0.0008), early erythroid progenitor colonies (â¼300%, P<0.0001) and reticulocytes (â¼500%, P=0.0007), and reduced erythrocyte lifespan (â¼50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg-1.day-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.
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Entrenamiento Aeróbico , Hematopoyesis , Células Madre Hematopoyéticas/enzimología , Peptidil-Dipeptidasa A/metabolismo , Resistencia Física , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Captopril/farmacología , Femenino , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Oligopéptidos/metabolismo , Condicionamiento Físico Animal , Dominios Proteicos , Ratas Wistar , Factores de TiempoRESUMEN
NEW FINDINGS: What is the central question of this study? Heat acclimation increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake (VO2 max) and performance in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. What is the main finding and its importance? We showed that heat acclimation increased VO2 max in a temperate environment but did not change markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle. ABSTRACT: Heat acclimation (HA) increases tolerance to exercise performed in the heat and may improve maximal oxygen uptake ( VÌO2max ) in temperate environments. However, it is unknown if HA affects the expression of proteins related to mitochondrial biogenesis and oxidative capacity in skeletal muscle. The purpose of this study was to investigate the effect of HA on skeletal muscle markers of mitochondrial biogenesis and oxidative phosphorylation in recreationally trained adults. Thirteen (7 males and 6 females) individuals underwent 10 days of HA. Participants performed two 45 min bouts of exercise (walking at 30-40% maximal velocity at 3% grade) with 10 min rest per session in a hot environment (â¼42°C and 30-50% relative humidity). VÌO2max , ventilatory thresholds (VT), and protein expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM), calcium/calmodulin-dependent protein kinase (CaMK), electron transport chain (ETC) complexes I-IV, and heat shock protein 72 (Hsp72) in skeletal muscle were measured pre- and post-HA. Comparing day 1 to day 10, HA was confirmed by lower resting core temperature (Tcore ) (P = 0.026), final Tcore (P < 0.0001), mean heart rate (HR) (P = 0.002), final HR (P = 0.003), mean ratings of perceived exertion (RPE) (P = 0.026) and final RPE (P = 0.028). Pre- to post-HA VÌO2max (P = 0.045) increased but VT1 (P = 0.263) and VT2 (P = 0.239) were unchanged. Hsp72 (P = 0.007) increased, but skeletal muscle protein expression (PGC-1α, P = 0.119; TFAM, P = 0.763; CaMK, P = 0.19; ETC I, P = 0.629; ETC II, P = 0.724; ETC III, P = 0.206; ETC IV, P = 0.496) were not affected with HA. HA during low-intensity exercise increased VÌO2max in a temperate environment and Hsp72 but it did not affect markers of mitochondrial biogenesis and oxidative phosphorylation in the skeletal muscle.
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Ejercicio Físico/fisiología , Proteínas del Choque Térmico HSP72/metabolismo , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Fosforilación Oxidativa , Aclimatación/fisiología , Adaptación Fisiológica/fisiología , Humanos , Biogénesis de Organelos , Consumo de Oxígeno/fisiologíaRESUMEN
PURPOSE: This study investigated the cardiometabolic health of overweight/obese untrained individuals in response to 8 weeks of HIIT and MICT using a field approach, and to 4 weeks of training cessation (TC). METHODS: Twenty-two subjects performed 8 weeks of moderate intensity continuous training (MICT-n = 11) or high-intensity interval training (HIIT-n = 11) (outdoor running), followed by 4 weeks of TC. Cardiorespiratory fitness, body composition, arterial blood pressure, glucose metabolism and blood lipids were measured pre-training (PRE), post-training (POST) and TC. RESULTS: HIIT improved eight indicators of cardiometabolic health ([Formula: see text], BMI, body fat, visceral fat, systolic blood pressure, total cholesterol, fasting glucose and triglycerides-p < 0.05) while MICT only three ([Formula: see text], BMI, and visceral fat-p < 0.05). After 4 weeks of TC, four positive adaptations from HIIT were negatively affected ( [Formula: see text], visceral fat, systolic blood pressure and total cholesterol-p < 0.05) and three in the MICT group ([Formula: see text], BMI and visceral fat, p < 0.05). CONCLUSION: Eight weeks of HIIT performed in a real-world setting promoted a greater number of positive adaptations in cardiometabolic health of individuals with overweight/obese compared to MICT. Most of the positive effects of the HIIT protocol were also found to be longer lasting and maintained after the suspension of high-intensity interval running for 4 weeks. Conversely, all positive effects of MICT protocols were reversed after TC.
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Capacidad Cardiovascular , Entrenamiento Aeróbico/métodos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Obesidad/terapia , Adulto , Glucemia/metabolismo , Presión Sanguínea , Composición Corporal , Entrenamiento Aeróbico/efectos adversos , Femenino , Frecuencia Cardíaca , Entrenamiento de Intervalos de Alta Intensidad/efectos adversos , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Consumo de OxígenoRESUMEN
BACKGROUND/OBJECTIVE: The integration of high-intensity interval training (HIIT) and circuit weight training (CWT) is seamless and practical for meeting recommended exercise guidelines. The purpose of this study was to determine the ideal combination of HIIT and CWT to elicit desired acute cardiorespiratory and metabolic responses in variables such as energy expenditure (EE), oxygen consumption (VO2), heart rate (HR), blood lactate (BLa-), excess post-exercise oxygen consumption (EPOC), rating of perceived exertion (RPE), and enjoyment. METHODS: Fourteen trained males (25.7⯱â¯4.4â¯yr) completed two exercise protocols matched for volume and recovery periods. On one day, participants performed six HIIT bouts prior to three rounds of a nine exercise CWT protocol (HIC). The second day (separated byâ¯≥â¯72â¯h) consisted of three rounds of three mini-circuits (three exercises per circuit) integrated with three HIIT bouts between the first and second and second and third mini-circuits (TRI). VO2, HR, and EE were monitored throughout both protocols. EPOC for a 20-min duration, [BLa-] (five time points), RPE, and enjoyment were measured post-exercise. RESULTS: Energy expenditure was significantly higher during the HIC compared to the TRI protocol (pâ¯=â¯.012), as well as EPOC (pâ¯=â¯.034). [BLa-] was significantly greater immediate-, 5min-, 10min- and 20min-post-exercise following HIC as compared to TRI. Mean values for HIC and TRI were similar (pâ¯>â¯.05) for HR and RPE. CONCLUSION: Performing HIIT prior to CWT elicits a higher metabolic perturbation compared to the TRI protocol. Although a significant EE difference was detected between the two trials, the practical difference (â¼20â¯kcal) between protocols indicates both protocols are similarly effective for caloric expenditure, metabolic and cardiorespiratory response.
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Choriocarcinoma is a rare condition, with an incidence of 1 in 30 to 40,000 pregnancies in the United States and Europe. In Mexico it is reported in 1 in 10,000 pregnancies. Wunderlich syndrome is a spontaneous perirenal hematoma, a very rare entity. This paper reports the case of a young patient with a history of molar pregnancy one year prior to admission, valuation due to fainting, generalized headache, spontaneous pain in the right flank and data of hypovolemic shock. Computed tomography reported right perirenal hematoma, normal uterus, two annexes with data of tecaluteinic cysts, beta human chorionic gonadotropin greater than 200,000 IU/mL. Patient was stabilized with crystalloid, blood products and right adrenal artery embolization. It was corroborated the brain, mediastinum and abdomen metastases. She was sent to a third level hospital, starting holocraneal radiotherapy, she had retroperitoneal bleeding and died a week later.
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Coriocarcinoma/diagnóstico , Hematoma/diagnóstico , Enfermedades Renales/diagnóstico , Adolescente , Coriocarcinoma/patología , Coriocarcinoma/terapia , Resultado Fatal , Femenino , Hematoma/patología , Humanos , Enfermedades Renales/patología , Metástasis de la Neoplasia , Embarazo , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Heart failure with preserved ejection fraction is a significant and growing public health problem, since it currently represents half of all patients with heart failure. Despite improvements in the understanding of the disease, there is no benefit form treatments tested at all. Advances in diagnostic imaging and invasive evaluation algorithms will allow a more accurate and early diagnosis so that treatment of earliest forms in the progression of the disease are applied since the potential for benefit may be higher. Although important progress has been made in our understanding of the pathophysiology, cardiac catheterization, and cellular of diastolic failure mechanisms and not diastolic mechanisms of disease, further research is required promptly to determine how best to address these anomalies to reduce the significant burden of morbidity and mortality in this form of heart failure, which is reaching pandemic proportions.
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Diástole , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico , Insuficiencia Cardíaca/diagnóstico , Frecuencia Cardíaca , Humanos , Miocitos Cardíacos/fisiologíaRESUMEN
The pyometra is a rare condition, with an incidence of less than 1%. In patients with cervical cancer, spontaneous rupture of pyometra manifests as a generalized peritonitis, which is extremely rare, in the literature only seven cases are described. This paper reports the case of a patient with a history of postmenopausal vaginal bleeding one month before her admission to the hospital; she attended because of acute abdomen. The CT scan reported air in the abdominal cavity and the uterus with air at the periphery, so she underwent an exploratory laparotomy in which purulent material was found with two perforations in the uterine fundus. She underwent total abdominal extrafacial hysterectomy with histopathological diagnosis of keratinizing squamous cell carcinoma, moderately differentiated.
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Carcinoma de Células Escamosas/complicaciones , Piómetra/complicaciones , Neoplasias del Cuello Uterino/complicaciones , Perforación Uterina/etiología , Abdomen Agudo/etiología , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Endometritis/complicaciones , Femenino , Humanos , Histerectomía , Metástasis Linfática , Ovariectomía , Peritonitis/complicaciones , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients' characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients' treatment adherence, thus preventing the long-term disability caused by psychotic disorders.
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CONTEXT: Numerous chronic conditions including obesity exhibit autophagic dysfunction. Association of immune cell autophagic marker regulation by body fat percentage (%BF) is unknown. OBJECTIVE: Investigate autophagy activity in peripheral blood mononuclear cells (PBMCs) of adults with distinct %BFs and obesity-related circulating inflammatory markers. MATERIALS AND METHODS: Sixteen individuals (eight males) with %BF above (n = 8, 36.9 ± 3.6 years, 27.1 ± 8.1%BF) and below (n = 8, 37.1 ± 3.7 years, 13.3 ± 3.7%BF) their age- and sex-specific 50th percentile value based on the American College Sports Medicine guidelines participated. Body fat percentage was calculated from hydrostatic weighing. PBMCs were isolated from venous blood, and PBMC autophagic flux markers (LC3-I, LC3-II, and p62) were measured via Western blot. CRP, resistin, leptin, and adiponectin were measured via ELISA. RESULTS: LC3-II/LC3-I ratio correlated with %BF (r=-0.56, p=.023). Insulin (p=.05) and CRP (p=.018) were higher in high %BF participants. DISCUSSION AND CONCLUSIONS: Autophagic activity markers in PBMCs correlate with %BF, but are not different between %BF groups.
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Resistencia a la Insulina , Leucocitos Mononucleares , Masculino , Adulto , Femenino , Humanos , Obesidad , Tejido Adiposo , AutofagiaRESUMEN
Sugarcane cutters are vulnerable to extreme heat and are at risk for heat-related illness and chronic kidney disease, potentially due to high heat strain. We performed a comprehensive assessment of the physiological demands of sugarcane cutters via measurements of metabolic, thermal, and cardiovascular responses. In addition, we assessed cross-shift changes in markers of kidney function. Nine male sugarcane cutters were monitored while working during the spring harvest season in Brazil. Core temperature (Tcore) and heart rate (HR) were continuously recorded, and oxygen consumption was measured during the work shift. Urine and blood samples were collected pre- and postwork shifts. Total sweat loss was calculated using body weight changes and adjusting for water ingestion and urine output. A wet-bulb globe temperature (WBGT) station was used to monitor environmental heat stress. WBGT was ≥30°C on 7 of the 8 study days. Mean and peak Tcore during the work shift were 37.96 ± 0.47°C and 38.60 ± 0.41°C, respectively, with all participants surpassing a Tcore of 38°C. Mean and peak HR during the work shift were 137 ± 14 and 164 ± 11 beats/min, respectively. Percent of maximal oxygen consumption was, on average, 53 ± 11%. Workers had a total sweat loss of 7.63 ± 2.31 L and ingested 6.04 ± 1.95 L of fluid. Kidney function (estimated glomerular filtration rate) was reduced from pre- to postwork shift (Δ -20 ± 18 mL·min·1.73 m2). We demonstrated that sugarcane cutters performing prolonged work during a period of high environmental heat stress display high levels of heat strain, high water turnover, and reduced kidney function.NEW & NOTEWORTHY We demonstrate that a shift of sugarcane cutting performed outdoors during the spring harvest season results in a high level of heat strain. In fact, all the studied workers sustained core temperatures above 38°C and heart rates above 75% of the measured maximum heart rate. Additionally, workers displayed a high water turnover with sweat loss close to 10% of their body weight. Finally, we report elevated muscle damage and reductions in kidney function following the work shift.
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Trastornos de Estrés por Calor , Saccharum , Humanos , Masculino , Brasil , Respuesta al Choque Térmico/fisiología , Agua , Calor , Peso CorporalRESUMEN
Chronic hyperglycemia is associated with low response to aerobic exercise training in rodent models and humans, including reduced aerobic exercise capacity and impaired oxidative remodeling in skeletal muscle. Here, we investigated whether glucose lowering with the sodium-glucose cotransporter 2 inhibitor (SGLT2i), canagliflozin (Cana; 30 mg/kg/day), could restore exercise training response in a model of hyperglycemia (low-dose streptozotocin [STZ]). Cana effectively prevented increased blood glucose in STZ-treated mice. After 6 weeks of voluntary wheel running, Cana-treated mice displayed improvements in aerobic exercise capacity, higher capillary density in striated muscle, and a more oxidative fiber-type in skeletal muscle. In contrast, these responses were blunted or absent in STZ-treated mice. Recent work implicates glucose-induced accumulation of skeletal muscle extracellular matrix (ECM) and hyperactivation of c-Jun N-terminal kinase (JNK)/SMAD2 mechanical signaling as potential mechanisms underlying poor exercise response. In line with this, muscle ECM accretion was prevented by Cana in STZ-treated mice. JNK/SMAD2 signaling with acute exercise was twofold higher in STZ compared with control but was normalized by Cana. In human participants, ECM accumulation was associated with increased JNK signaling, low VO2peak, and impaired metabolic health (oral glucose tolerance test-derived insulin sensitivity). These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by cotherapy with SGLT2i.
Asunto(s)
Hiperglucemia , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Canagliflozina/farmacología , Canagliflozina/uso terapéutico , Matriz Extracelular/metabolismo , Glucosa/metabolismo , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/prevención & control , Ratones , Actividad Motora , Músculo Esquelético/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , EstreptozocinaRESUMEN
Vaccination is widely considered the most effective preventative strategy to protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. An individual's exercise habits, and physical fitness have been shown to impact the immune response following vaccination using traditional vaccine platforms, but their effects are not well characterized following administration of newer vaccination technology (mRNA vaccines). We investigated these effects on the magnitude of antibody responses following SARS-CoV-2 mRNA vaccination while accounting for known covariates (age, sex, time since vaccination, and the type of vaccine administered). Adults of varying fitness levels (18-65 years; N = 50) who had received either the Moderna or Pfizer SARS-CoV-2 mRNA vaccine between 2 weeks and 6 months prior, completed health history and physical activity questionnaires, had their blood drawn, body composition, cardiorespiratory fitness, and strength assessed. Multiple linear regressions assessed the effect of percent body fat, hand grip strength, cardiorespiratory fitness, and physical activity levels on the magnitude of receptor binding domain protein (RBD) and spike protein subunit 1 (S1) and 2 (S2) while accounting for known covariates. Body fat percentage was inversely associated with the magnitude of S1 (p = 0.006, ß = - 366.56), RBD (p = 0.003, ß = - 249.30), and S2 (p = 0.106, ß = - 190.08) antibodies present in the serum following SARS-CoV-2 mRNA vaccination. Given the increasing number of infections, variants, and the known waning effects of vaccination, future mRNA vaccinations such as boosters are encouraged to sustain immunity; reducing excess body fat may improve the efficacy of these vaccinations.